Cardioplegia is an elective stopping of cardiac activity temporarily by injection of chemicals, selective hypothermia, or electrical stimuli. Presently, the most widely employed method of cardioplegia is by injection of potassium chloride (KCl). KCl causes reversible arrest of the beating and blood pumping activities of the heart. In addition to this desired effect, KCl injection has a number of undersirable side effects. For example, KCl treatment induces a transient state of sustained muscular contracture which, in turn, results in the rapid depletion of cellular energy stores (ATP and PCr). As a consequence, the permissible duration of cardiac arrest is shortened by this accelerated expenditure of cellular energy.
Following the transient contracture and rapid depletion of energy stores, there is a further, gradual, depletion of energy stores due to basal metabolism. When the later causes energy stores to fall sufficiently low, the muscle cells can no longer keep calcium ions pumped out of the myoplasm. This triggers a renewed activation of muscular contraction which rapidly further reduces the energy stores and leads to cell death and rigor mortis. Additionally, surgery performed on muscle arrested but still capable of undergoing contraction can result in contracture-induced self destruction. Self-destruction results when the mechanical forces produced by one cell during contracture are transmitted to adjacent, previously undamaged cells causing them to be damaged and to go into contracture. In this way, the original damage can be propogated through the bulk of the muscle.
Among the other KCl induced side effect are depolarization, loss of cellular excitability, and major shifts in cellular electrolyte balance. Such side effects render the electrocardiogram useless as a diagnostic aid during the period of cardioplegia.
A compound which could induce cardioplegia without these undesirable side effects would be useful as a cardioplegic agent.